RESUMEN
Background: Both dabrafenib/trametinib (D/T) and anti-PD-1 monotherapy (PD-1) are approved adjuvant therapies for patients with stage III BRAF V600-mutant melanoma. However, there is still a lack of head-to-head comparative data. We aimed to describe efficacy and toxicity outcomes for these two standard therapies across melanoma centers. Methods: This multicenter, retrospective cohort study was conducted in 15 melanoma centers in Australia, China, Germany, Italy, Japan, UK, and US. We included adult patients with resected stage III BRAF V600-mutant melanoma who received either adjuvant D/T or PD-1 between Jul 2015 and Oct 2022. The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), recurrence pattern and toxicity. Findings: We included 598 patients with stage III BRAF V600-mutant melanoma who received either adjuvant D/T (n = 393 [66%]) or PD-1 (n = 205 [34%]) post definitive surgery between Jul 2015 and Oct 2022. At a median follow-up of 33 months (IQR 21-43), the median RFS was 51.0 months (95% CI 41.0-not reached [NR]) in the D/T group, significantly longer than PD-1 (44.8 months [95% CI 28.5-NR]) (univariate: HR 0.66, 95% CI 0.50-0.87, P = 0.003; multivariate: HR 0.58, 95% CI 0.39-0.86, P = 0.007), with comparable OS with PD-1 (multivariate, HR 0.90, 95% CI 0.48-1.70, P = 0.75). Similar findings were observed using a restricted-mean-survival-time model. Among those who experienced recurrence, the proportion of distant metastases was higher in the D/T cohort. D/T had a higher incidence of treatment modification due to adverse events (AEs) than PD-1, but fewer persistent AEs. Interpretation: In patients with stage III BRAF V600-mutant melanoma post definitive surgery, D/T yielded better RFS than PD-1, with higher transient but lower persistent toxicity, and comparable OS. D/T seems to provide a better outcome compared with PD-1, but a longer follow-up and ideally a large prospective trial are needed. Funding: Dr. Xue Bai was supported by the Beijing Hospitals Authority Youth Programme (QMS20211101) for her efforts devoted to this study. Dr. Keith T. Flaherty was funded by Adelson Medical Research Foundation for the efforts devoted to this study.
RESUMEN
Introduction: Markers of inflammation such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) have been found to be associated with survival in cancer patients. The aim of the current study was to establish the prognostic significance of simple laboratory markers of systemic inflammation in paediatric patients diagnosed with Wilms tumour (WT). Additionally, we aimed to compare the complete blood count (CBC) parameters of WT patients and the non-oncological control group. Material and methods: The study group included 88 children diagnosed with WT. Clinicopathological data, as well as CBC, C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels at diagnosis, were obtained. Additionally, the laboratory results of 62 healthy control paediatric patients were collected. Uni- and multivariate proportional Cox's hazard analyses were computed to create a model predicting relapse-free survival (RFS) and overall survival (OS) in the study group. Results: High CRP, LDH, and NLR were associated with a higher stage of WT and shorter RFS, whereas all parameters correlated with OS. In multivariate analysis, only LDH levels had adverse significance in predicting RFS. C-reactive protein and LMR retained their prognostic value in the multivariate model predicting OS. Comparing the WT group with controls, high LDH, high CRP, high NLR, and high PLR were associated with WT presence. Conclusions: Preoperative LDH, CRP, NLR, PLR, and LMR have significant prognostic value in patients with WT independently of age and stage. Combined low CRP and high LMR identified the group of patients with excellent OS. Patients with high LDH were characterized by the highest risk of relapse.